Combination of bacteriophages and vancomycin in a co-delivery hydrogel for localized treatment of fracture-related infections

oleh: Baixing Chen, Luis Ponce Benavente, Marco Chittò, Virginia Post, Caroline Constant, Stephan Zeiter, Pamela Nylund, Matteo D’Este, Mercedes González Moreno, Andrej Trampuz, Jeroen Wagemans, Rob Lavigne, Jolien Onsea, R. Geoff Richards, Willem-Jan Metsemakers, T. Fintan Moriarty

Format: Article
Diterbitkan: Nature Portfolio 2024-08-01

Deskripsi

Abstract Fracture-related infections (FRIs), particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA), are challenging to treat. This study designed and evaluated a hydrogel loaded with a cocktail of bacteriophages and vancomycin (1.2 mg/mL). The co-delivery hydrogel showed 99.72% reduction in MRSA biofilm in vitro. The hydrogel released 54% of phages and 82% of vancomycin within 72 h and maintained activity for eight days, in vivo the co-delivery hydrogel with systemic antibiotic significantly reduced bacterial load by 0.99 log10 CFU compared to controls, with active phages detected in tissues at euthanasia (2 × 103 PFU/mL). No phage resistance was detected in the phage treatment groups, and serum neutralization resulted in only a 20% reduction in phage count. In this work, we show that a phage-antibiotic co-delivery system via CMC hydrogel is a promising adjunct to systemic antibiotic therapy for MRSA-induced FRI, highlighting its potential for localized, sustained delivery and improved treatment outcomes.